Decoding the interplay between m 6 A modification and stress granule stability by live-cell imaging.

Autor: Li Q; Shenzhen Bay Laboratory, Shenzhen 518132, China., Liu J; Shenzhen Bay Laboratory, Shenzhen 518132, China., Guo L; Shenzhen Bay Laboratory, Shenzhen 518132, China.; School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China., Zhang Y; Shenzhen Bay Laboratory, Shenzhen 518132, China., Chen Y; Shenzhen Bay Laboratory, Shenzhen 518132, China.; Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China., Liu H; Shenzhen Bay Laboratory, Shenzhen 518132, China.; State Key Laboratory of Crop Stress Biology for Arid Areas, College of Life Sciences, Northwest A&F University, Yangling 712100, Shaanxi, China., Cheng H; Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, College of Bioengineering, Chongqing University, Chongqing 400030, China., Deng L; Shenzhen Bay Laboratory, Shenzhen 518132, China., Qiu J; Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, College of Bioengineering, Chongqing University, Chongqing 400030, China., Zhang K; Shenzhen Bay Laboratory, Shenzhen 518132, China., Goh WSS; Shenzhen Bay Laboratory, Shenzhen 518132, China., Wang Y; Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA., Peng Q; Shenzhen Bay Laboratory, Shenzhen 518132, China.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2024 Nov 15; Vol. 10 (46), pp. eadp5689. Date of Electronic Publication: 2024 Nov 15.
DOI: 10.1126/sciadv.adp5689
Abstrakt: N 6 -methyladenosine (m 6 A)-modified mRNAs and their cytoplasmic reader YTHDFs are colocalized with stress granules (SGs) under stress conditions, but the interplay between m 6 A modification and SG stability remains unclear. Here, we presented a spatiotemporal m 6 A imaging system (SMIS) that can monitor the m 6 A modification and the translation of mRNAs with high specificity and sensitivity in a single live cell. SMIS showed that m 6 A-modified reporter mRNAs dynamically enriched into SGs under arsenite stress and gradually partitioned into the cytosol as SG disassembled. SMIS revealed that knockdown of YTHDF2 contributed to SG disassembly, resulting in the fast redistribution of mRNAs from SGs and rapid recovery of stalled translation. The mechanism is that YTHDF2 can regulate SG stability through the interaction with G3BP1 in m 6 A-modified RNA-dependent manner. Our results suggest a mechanism for the interplay between m 6 A modification and SG through YTHDF2 regulation.
Databáze: MEDLINE